Mass spectrometry (MS) describes a variety of instrumental methods of qualitative and quantitative analysis that enable sample components to be resolved according to their mass-to-charge ratios. For this purpose, a mass spectrometer converts the components of a sample into ions, sorts or separates the ions based on their mass-to-charge ratios, and processes the resulting ion output (for example, ion current, flux, beam, et cetera) as needed to produce a mass spectrum. Typically, a mass spectrum is a series of peaks indicative of the relative abundances of charged components as a function of mass-to-charge ratio. The term “mass-to-charge” is often expressed as m/z or m/e, or simply “mass” given that the charge z or e often has a value of 1. The information represented by the ion output can be encoded as electrical signals through the use of an appropriate transducer to enable data processing by both analog and digital techniques. An ion detector is a type of transducer that converts ion current to electrical current and thus is commonly employed in an MS system.
Insofar as the present disclosure is concerned, MS systems are generally known and need not be described in detail. Briefly, a typical MS system generally includes a sample inlet system, an ion source or ionization system, a mass analyzer (also termed a mass sorter or mass separator) or multiple mass analyzers, an ion detector, a signal processor, and readout/display means. Additionally, the modern MS system includes an electronic controller such as a computer or other electronic processor-based device for controlling the functions of one or more components of the MS system, storing information produced by the MS system, providing libraries of molecular data useful for analysis, and the like. The electronic controller may include a main computer that includes a terminal, console or the like for enabling interface with an operator of the MS system, as well as one or more modules or units that have dedicated functions such as data acquisition and manipulation. The MS system also includes a vacuum system to enclose the mass analyzer(s) in a controlled, evacuated environment. In addition to the mass analyzer(s), depending on design, all or part of the sample inlet system, ion source, and ion detector may also be enclosed in the evacuated environment.
In operation, the sample inlet system introduces a small amount of sample material to the ion source, which may be integrated with the sample inlet system depending on design. In hyphenated techniques, the sample inlet system may be the output of an analytical separation instrument such as a gas chromatographic (GC) instrument, a liquid chromatographic (LC) instrument, a capillary electrophoresis (CE) instrument, a capillary electrochromatography (CEC) instrument, or the like. The ion source converts components of the sample material into a stream of positive and negative ions. One ion polarity is then accelerated into the mass analyzer. The mass analyzer separates the ions according to their respective mass-to-charge ratios. Many mass analyzers are capable of distinguishing between very minute differences in m/z ratio among the ions being analyzed. The mass analyzer produces a flux of ions resolved according to m/z ratio and the ions are collected at the ion detector.
In other hyphenated techniques, such as tandem MS or MS/MS, more than one mass analyzer (and more than one type of mass analyzer) may be used. As one example, an ion source may be coupled to a multipole (for example, quadrupole) structure that acts as a first stage of mass separation to isolate molecular ions of a mixture. The first analyzer may in turn be coupled to another multipole structure (normally operated in an RF-only mode) that performs a collision-focusing function and is often termed a collision chamber or collision cell. A suitable collision gas such as argon is injected into the collision cell to cause fragmentation of the ions and thereby produce daughter ions. This second multipole structure may in turn be coupled to yet another multipole structure that acts as a second stage of mass separation to scan the daughter ions. Finally, the output of the second stage is coupled to an ion detector. Instead of multipole structures, magnetic and/or electrostatic sectors may be employed. Other examples of MS/MS systems include the Varian Inc. 1200 series of triple-quadrupole GC/MS systems commercially available from Varian, Inc., Palo Alto, Calif., and the implementations disclosed in U.S. Pat. No. 6,576,897, assigned to the assignee of the present disclosure.
As previously noted, the ion detector functions as a transducer that converts the mass-discriminated ionic information into electrical signals suitable for processing/conditioning by the signal processor, storage in memory, and presentation by the readout/display means. A typical ion detector includes, as a first stage, an ion-to-electron conversion device. Ions from the mass analyzer are focused toward the ion-to-electron conversion device by means of an electrical field and/or electrode structures that serve as ion optics. The electrical and structural ion optics are preferably designed so as to separate the ion beam from any neutral particles and electromagnetic radiation that may also be discharged from the mass analyzer, thereby reducing background noise and increasing the signal-to-noise (S/N) ratio. The ion-to-electron conversion device typically includes a surface that emits secondary electrons in response to impingement by ions, and the conversion efficiency can be different for each mass and its energy state at the time of impact. The ion conversion stage may be followed by an electron multiplier stage. The electron multiplier typically is a continuous-dynode type or a discrete-dynode type. In the continuous-dynode type, a voltage potential is impressed across the length of a containment structure of the electron multiplier. Ions enter the structure and strike an interior surface of the structure, which results in the surface emitting electrons (that is, the ion-to-electron conversion stage). The electrons then skip along the surface. With each impact of the electrons on the surface, additional electrons are liberated from the surface. The structure of the continuous-dynode electron multiplier is shaped to facilitate this cascading of electrons. By comparison, the discrete-dynode electron multiplier has a series of individual dynodes, with the first electrode constituting the ion-to-electron conversion stage. Each dynode is held at a successively higher voltage. Thus, after the ion input is converted into electrons, the electrons impact each dynode in succession. Each dynode has a surface that causes additional electrons to be emitted upon impact by incoming electrons. The dynodes are arranged in space to ensure impingement by the multiplying flux of electrons. Either type of electron multiplier typically includes an end electrode that serves as an anode for collecting the multiplied flux of electrons and transmitting an output electrical current to subsequent processes.
A photomultiplier may be substituted for an electron multiplier and operated in a similar manner. For example, a photomultiplier tube (PMT) typically includes a photo cathode surface that emits electrons when exposed to radiation, and a series of dynodes to achieve a cascading of electrons for ultimate collection at an anode and subsequent amplification and measurement.
Electron multipliers such as those just described provide a current gain that may range, for example, from 103 to 109. In the present context, the gain of the electron multiplier is the ratio of its output electrical current to its input ion current. Hence, the output of an ion detector equipped with an electron multiplier is an amplified electrical current proportional to the intensity of the ion current fed to the ion detector and the gain of the electron multiplier. This output current can be processed as needed to yield a mass spectrum that can be displayed or printed by the readout/display means. A trained analyst can then interpret the mass spectrum to obtain information regarding the sample material processed by the MS system.
Like many analytical techniques, figures of merit are associated with the performance of a mass spectrometer. From the above description of the function of the ion detector, it can be seen that the performance of the ion detector, and particularly the electron multiplier portion, can significantly affect the performance of the mass spectrometer as a whole. Two important figures of merit are sensitivity and dynamic range, which in the present context can provide a measure of the performance of the ion detector employed in an MS system. Insofar as these terms relate to ion detection, for a set gain, sensitivity may be characterized as being the level of output electrical current for a given input ion current. To optimize sensitivity, the gain of the electron multiplier is increased until the signal exceeds all other sources of noise, with an S/N of about 5:1. Ion detectors equipped with electron multipliers are generally more sensitive than other types of ion collectors such as Faraday cups due to the internal amplification provided by the electron multiplier. Dynamic range may be characterized as being the range of output electrical current values over which the electron multiplier will provide a linear response. Dynamic range may be adversely affected by the signal processing circuitry that follows the ion detector. For example, analog-to-digital converters (ADCs) are often provided to transform the analog signals generated by the ion detector to digital signals in order to take advantage of computerized data acquisition hardware and software. In this case, the dynamic range of an ion detector system is usually limited to the range of the ADC. To compensate for this limitation, a user of an MS system has traditionally adjusted the gain of the electron multiplier to optimize either sensitivity or dynamic range. Gain is adjusted by adjusting the high-voltage supply to the electron multiplier. However, increasing sensitivity such as by increasing gain may prematurely stress or age the specialized material that comprises the surfaces of the electron multiplier utilized for electron emission. These surfaces are designed to be operated at a gain that results in an optimum output current providing a good S/N ratio and reasonable service life. Other problems have been found in attempting to optimize sensitivity and dynamic range. For instance, the means taken for extending dynamic range may reduce sensitivity, lower the precision of detected mass peaks, narrow the bandwidth of amplifiers employed in signal processing, and/or limit the maximum scan speed of the mass analyzer. Moreover, there has not existed a sufficient method for increasing both dynamic range and sensitivity, or at least increasing dynamic range without adversely affecting sensitivity. Accordingly, there continues to be a need for improved techniques for optimizing sensitivity and dynamic range in mass spectrometers utilizing electron multipliers.